ω-Aryl-13,14-didehydro-PGE compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,739,filed Feb. 13, 1976, now issued as U.S. Pat. No. 4,029,681 on June 14,1977.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,029,681, issued June 14, 1977.

I claim:
 1. A prostaglandin analog of the formula: ##STR1## wherein D is##STR2## whereyn Y₁ is --C.tbd.C--; wherein Z₆ is(1) cis--CH═CH--CH₂--(CH₂)_(g) --CH₂ --, (2) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (3)cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --, (4) --(CH₂)₃ --(CH₂)_(g) --CH₂ --,or (5)--(CH₂)₃ --(CH₂)_(g) --CF₂ --, wherein g is one, 2, or 3: whereinZ₃ is oxa or methylene; wherein T is chloro, fluoro, trifluoromethyl,alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbonatoms, inclusive, and s is zero, one, 2, or 3, the various T's being thesame or different, with the proviso that not more than two T's are otherthan alkyl, with the further proviso that Z₃ is oxa only when R₃ and R₄are hydrogen or methyl, being the same or different; wherein M₁ is##STR3## wherein R₅ and R₆ are hydrogen or methyl, with the proviso thatone of R₅ and R₆ is methyl only when the other is hydrogen; wherein L₁is ##STR4## or a mixture of ##STR5## wherein R₃ and R₄ are hydrogen,methyl, or fluoro, being the same or different, with the proviso thatone of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro andwherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl, phenyl substituted with one, two, or threechloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 2. A compound according to claim 1,wherein D is ##STR6##
 3. A compound according to claim 1, wherein D is##STR7##
 4. A compound according to claim 3, wherein Z₃ is methylene. 5.A compound according to claim 4, wherein s is zero or one and T ischloro, fluoro, or trifluoromethyl.
 6. A compound according to claim 3,wherein Z₃ is oxa.
 7. A compound according to claim 6, wherein s iszero.
 8. A compound according to claim 6, wherein s is zero or one and Tis chloro, fluoro, or trifluoromethyl.
 9. A compound according to claim8, wherein Z₆ is cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 10. A compoundaccording to claim 8, wherein Z₆ is cis--CH₂ CH═CH--(CH₂)_(g) --CH₂ --.11. A compound according to claim 8, wherein Z₆ is cis--CH═CH--CH₂--(CH₂)_(g) --CH₂ --.
 12. A compound according to claim 11, wherein M₁is ##STR8##
 13. A compound according to claim 12, wherein g is one. 14.A compound according to claim 13, wherein R₃, R₄, R₅, and R₆ are allhydrogen. 15.15-epi-16-phenoxy-17,18,19,20-tetranor-13,14-didehydroPGE₂, methylester, a compound according to claim
 14. 16. A compound according toclaim 11, wherein M₁ is ##STR9##
 17. A compound according to claim 16,wherein g is three.
 18. A compound according to claim 16, wherein g isone.
 19. A compound according to claim 18, wherein R₃ and R₄ are bothhydrogen.
 20. A compound according to claim 19, wherein R₅ is methyl.21. 16-Phenoxy-17,18,19,20-tetranor-15-methyl-13,14-didehydro-PGE₂, acompound according to claim
 20. 22.16-Phenoxy-17,18,19,20-tetranor-15-methyl-13,14-didehydro-PGE₂, methylester, a compound according to claim
 20. 23. A compound according toclaim 135, wherein R₆ is methyl. 24.16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₂, 15-methyl ether, acompound according to claim
 23. 25.16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₂, methyl ester,15-methyl ether, a compound according to claim
 23. 26. A compoundaccording to claim 19, wherein R₅ and R₆ are both hydrogen. 27.16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₂, a compoundaccording to claim
 26. 28.16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₂, methyl ester, acompound according to claim
 26. 29. A compound according to claim 18,wherein at least one of R₃ and R₄ is methyl.
 30. A compound according toclaim 29, wherein R₃ and R₄ are both methyl.
 31. A compound according toclaim 30, wherein R₅ is methyl. 32.16-Phenoxy-18,19,20-trinor-15,16-dimethyl-13,14-didehydro-PGE₂, methylester, a compound according to claim
 31. 33. A compound according toclaim 30, wherein R₆ is methyl. 34.16-Phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGE₂, methyl ester,15-methyl ester, a compound according to claim
 33. 35. A compoundaccording to claim 30, wherein R₅ and R₆ are both hydrogen. 36.16-Phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGE₂, a compoundaccording to claim
 35. 37.16-Phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGE₂, methyl ester,a compound according to claim 35.